Elsevier

The Lancet

Volume 378, Issue 9804, 12–18 November 2011, Pages 1727-1740
The Lancet

Seminar
Non-small-cell lung cancer

https://doi.org/10.1016/S0140-6736(10)62101-0Get rights and content

Summary

In the decade since the last Lancet Seminar on lung cancer there have been advances in many aspects of the classification, diagnosis, and treatment of non-small-cell lung cancer (NSCLC). An international panel of experts has been brought together to focus on changes in the epidemiology and pathological classification of NSCLC, the role of CT screening and other techniques that could allow earlier diagnosis and more effective treatment of the disease, and the recently introduced seventh edition of the TNM classification and its relation to other prognostic factors such as biological markers. We also describe advances in treatment that have seen the introduction of a new generation of chemotherapy agents, a proven advantage to adjuvant chemotherapy after complete resection for specific stage groups, new techniques for the planning and administration of radiotherapy, and new surgical approaches to assess and reduce the risks of surgical treatment.

Section snippets

Advances in pathology

The last Lancet Seminar on non-small-cell lung cancer (NSCLC) was published in 2000, with no mention of the advancing molecular age,1 and although the 2004 WHO classification of lung tumours introduced relevant genetic data,2 rapid development in this area has necessitated an almost immediate update, specifically relating to adenocarcinoma and diagnosis on the basis of biopsies and cytological material.3 A key aspect of this recent update was the multidisciplinary and international composition

Advances in early diagnosis

Routine screening for lung cancer is not currently recommended by any major medical organisation. Several phase 2 non-randomised trials of CT screening of high-risk individuals (current or former smokers with 20 pack-years of smoking) have yielded enticing results.20, 21, 22 They have shown that CT screening detects small-sized lung cancers of 12–15 mm in diameter. Chest radiographs have been shown to miss 70–80% of the cancers that are detected by CT. In prevalence studies, 60–80% of detected

Prognostic factors

The assessment of prognosis is an important factor affecting the selection of appropriate treatment for each individual case. The variables that are associated with prognosis can be grouped into categories: tumour-related, such as primary site, cell type, and extent of disease; patient-related, such as performance status, comorbidity, and sex; and environmental factors, such as nutrition and the choice and quality of treatment.40 These variables can be useful individually or combined to form a

Advances in surgical treatment

Technological advances and knowledge generated from clinical trials continue to improve our understanding of the role of surgery in staging, selection, and surgical management of patients with lung cancer. Mediastinoscopy and mediastinal lymph-node biopsy was widely done for the diagnosis and staging of lung cancer, but with increasing availability and use of PET and PET/CT, mediastinoscopy became reserved to screening for false-positive results on PET so as not to deny suitable patients the

Advances in chemotherapy in adjuvant, induction, and multimodal settings

Despite optimum surgical management, the 5-year survival rate of resected NSCLC ranges from 25% to 73% according to pathological stage. In a meta-analysis72 published in 1995, a 13% reduction in the risk of death was reported, suggesting an absolute benefit of 5% at 5 years with adjuvant chemotherapy.72 These results constituted the rationale for a new generation of randomised studies with platin-based regimens.73, 74, 75, 76, 77, 78

The LACE meta-analysis79 pooled 4584 patients accrued in five

First-line treatment

Chemotherapy remains the mainstay of treatment for advanced stage IIIB and IV NSCLC (table 2).92, 93, 94, 95, 96, 97, 98 A platinum-based doublet is recommended for fit patients, and single agents can be offered in elderly patients or poor performance subsets.99, 100 Selection of therapy was not based on histological subtype until recently, when the multitargeted antifolate agent pemetrexed was shown to be less active in patients with squamous cancers than in other types of disease; approval of

Advances in radiotherapy

Radiotherapy has important roles in both curative and palliative treatment of NSCLC. An estimated 75% of patients with NSCLC might benefit from radiotherapy.116 Recent advances in radiotherapy for NSCLC have been more strongly affected by developments in technology than by an improved understanding of the radiobiology of the disease.

Curative radiotherapy might be indicated in patients with good performance status (Eastern Cooperative Oncology Group status 0–1) and inoperable disease localised

Search strategy and selection criteria

The literature search for each section was based on a search of Medline and PubMed for the years since the previous Lancet Seminars on this topic (2000 and 2005) and 2009 inclusive. We searched for English language articles only, using the keywords “carcinoma, non-small cell” and the specific terms used in the title of each section. Additional references were taken from review articles and the individual authors' own publications.

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